For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
3
views
59
references
 Top references
cited by
4
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      397
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Protective Effects of Flavone from Tamarix aphylla against CCl 4-Induced Liver Injury in Mice Mediated by Suppression of Oxidative Stress, Apoptosis and Angiogenesis

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          The current study aimed to investigate, for the first time, the beneficial effects of 3,5-dihydroxy-4′,7-dimethoxyflavone isolated from Tamarix aphylla L. against liver injury in mice. Liver injury was induced by intraperitoneal (i.p.) injection of carbon tetrachloride (CCl 4) at a dose of 0.4 mL/kg mixed in olive oil at ratio (1:4) twice a week for 6 consecutive weeks. The administration of CCl 4 caused significant histopathological changes in liver tissues while the pre-treatment with the flavone at dose of 10 and 25 mg/kg ameliorated the observed liver damages. Also, it markedly reduced hepatic malondialdehyde (MDA) level as well as increased the activities of liver superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (Gpx) compared with their recorded levels in CCl 4 model group. Moreover, the immunohistochemical analysis demonstrated the enhancement in the protein level of B-cell lymphoma-2 (Bcl-2) while the protein levels of cysteine-aspartic acid protease-3 (caspase-3), Bcl-2-associated x protein (Bax), transforming growth factor-β1 (TGF-β1) and CD31 were suppressed following the flavone treatement. These results suggest that the flavone can inhibit liver injury induced in mice owning to its impact on the oxidation, apoptotic and angiogenesis mechanisms. Further pharmacological investigations are essential to determine the effectiveness of the flavone in human.

          Related collections

          Most cited references59

          • Record: found
          • Abstract: found
          • Article: not found

          Hepatotoxicity and mechanism of action of haloalkanes: carbon tetrachloride as a toxicological model.

          Lutz Weber, Meinrad Boll, Andreas Stampfl (2003)
          The use of many halogenated alkanes such as carbon tetrachloride (CCl4), chloroform (CHCl3) or iodoform (CHI3), has been banned or severely restricted because of their distinct toxicity. Yet CCl4 continues to provide an important service today as a model substance to elucidate the mechanisms of action of hepatotoxic effects such as fatty degeneration, fibrosis, hepatocellular death, and carcinogenicity. In a matter of dose,exposure time, presence of potentiating agents, or age of the affected organism, regeneration can take place and lead to full recovery from liver damage. CCl4 is activated by cytochrome (CYP)2E1, CYP2B1 or CYP2B2, and possibly CYP3A, to form the trichloromethyl radical, CCl3*. This radical can bind to cellular molecules (nucleic acid, protein, lipid), impairing crucial cellular processes such as lipid metabolism, with the potential outcome of fatty degeneration (steatosis). Adduct formation between CCl3* and DNA is thought to function as initiator of hepatic cancer. This radical can also react with oxygen to form the trichloromethylperoxy radical CCl3OO*, a highly reactive species. CCl3OO* initiates the chain reaction of lipid peroxidation, which attacks and destroys polyunsaturated fatty acids, in particular those associated with phospholipids. This affects the permeabilities of mitochondrial, endoplasmic reticulum, and plasma membranes, resulting in the loss of cellular calcium sequestration and homeostasis, which can contribute heavily to subsequent cell damage. Among the degradation products of fatty acids are reactive aldehydes, especially 4-hydroxynonenal, which bind easily to functional groups of proteins and inhibit important enzyme activities. CCl4 intoxication also leads to hypomethylation of cellular components; in the case of RNA the outcome is thought to be inhibition of protein synthesis, in the case of phospholipids it plays a role in the inhibition of lipoprotein secretion. None of these processes per se is considered the ultimate cause of CCl4-induced cell death; it is by cooperation that they achieve a fatal outcome, provided the toxicant acts in a high single dose, or over longer periods of time at low doses. At the molecular level CCl4 activates tumor necrosis factor (TNF)alpha, nitric oxide (NO), and transforming growth factors (TGF)-alpha and -beta in the cell, processes that appear to direct the cell primarily toward (self-)destruction or fibrosis. TNFalpha pushes toward apoptosis, whereas the TGFs appear to direct toward fibrosis. Interleukin (IL)-6, although induced by TNFalpha, has a clearly antiapoptotic effect, and IL-10 also counteracts TNFalpha action. Thus, both interleukins have the potential to initiate recovery of the CCl4-damaged hepatocyte. Several of the above-mentioned toxication processes can be specifically interrupted with the use of antioxidants and mitogens, respectively, by restoring cellular methylation, or by preserving calcium sequestration. Chemicals that induce cytochromes that metabolize CCl4, or delay tissue regeneration when co-administered with CCl4 will potentiate its toxicity thoroughly, while appropriate CYP450 inhibitors will alleviate much of the toxicity. Oxygen partial pressure can also direct the course of CCl4 hepatotoxicity. Pressures between 5 and 35 mmHg favor lipid peroxidation, whereas absence of oxygen, as well as a partial pressure above 100 mmHg, both prevent lipid peroxidation entirely. Consequently, the location of CCl4-induced damage mirrors the oxygen gradient across the liver lobule. Mixed halogenated methanes and ethanes, found as so-called disinfection byproducts at low concentration in drinking water, elicit symptoms of toxicity very similar to carbon tetrachloride, including carcinogenicity.
          Article 0 comments Cited 374 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: found
            Is Open Access

            Mitochondrial apoptosis: killing cancer using the enemy within

            J. López, S W G Tait (2015)
            Apoptotic cell death inhibits oncogenesis at multiple stages, ranging from transformation to metastasis. Consequently, in order for cancer to develop and progress, apoptosis must be inhibited. Cell death also plays major roles in cancer treatment, serving as the main effector function of many anti-cancer therapies. In this review, we discuss the role of apoptosis in the development and treatment of cancer. Specifically, we focus upon the mitochondrial pathway of apoptosis—the most commonly deregulated form of cell death in cancer. In this process, mitochondrial outer membrane permeabilisation or MOMP represents the defining event that irrevocably commits a cell to die. We provide an overview of how this pathway is regulated by BCL-2 family proteins and describe ways in which cancer cells can block it. Finally, we discuss exciting new approaches aimed at specifically inducing mitochondrial apoptosis in cancer cells, outlining their potential pitfalls, while highlighting their considerable therapeutic promise.
            Article 0 comments Cited 242 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Update on uses and properties of citrus flavonoids: new findings in anticancer, cardiovascular, and anti-inflammatory activity.

              O Benavente-García, J. Castillo (2008)
              Significantly, much of the activity of Citrus flavonoids appears to impact blood and microvascular endothelial cells, and it is not surprising that the two main areas of research on the biological actions of Citrus flavonoids have been inflammation and cancer. Epidemiological and animal studies point to a possible protective effect of flavonoids against cardiovascular diseases and some types of cancer. Although flavonoids have been studied for about 50 years, the cellular mechanisms involved in their biological action are still not completely known. Many of the pharmacological properties of Citrus flavonoids can be linked to the abilities of these compounds to inhibit enzymes involved in cell activation. Attempts to control cancer involve a variety of means, including the use of suppressing, blocking, and transforming agents. Suppressing agents prevent the formation of new cancers from procarcinogens, and blocking agents prevent carcinogenic compounds from reaching critical initiation sites, while transformation agents act to facilitate the metabolism of carcinogenic components into less toxic materials or prevent their biological actions. Flavonoids can act as all three types of agent. Many epidemiological studies have shown that regular flavonoid intake is associated with a reduced risk of cardiovascular diseases. In coronary heart disease, the protective effects of flavonoids include mainly antithrombotic, anti-ischemic, anti-oxidant, and vasorelaxant. It is suggested that flavonoids decrease the risk of coronary heart disease by three major actions: improving coronary vasodilatation, decreasing the ability of platelets in the blood to clot, and preventing low-density lipoproteins (LDLs) from oxidizing. The anti-inflammatory properties of the Citrus flavonoids have also been studied. Several key studies have shown that the anti-inflammatory properties of Citrus flavonoids are due to its inhibition of the synthesis and biological activities of different pro-inflammatory mediators, mainly the arachidonic acid derivatives, prostaglandins E 2, F 2, and thromboxane A 2. The anti-oxidant and anti-inflammatory properties of Citrus flavonoids can play a key role in their activity against several degenerative diseases and particularly brain diseases. The most abundant Citrus flavonoids are flavanones, such as hesperidin, naringin, or neohesperidin. However, generally, the flavones, such as diosmin, apigenin, or luteolin, exhibit higher biological activity, even though they occur in much lower concentrations. Diosmin and rutin have a demonstrated activity as a venotonic agent and are present in several pharmaceutical products. Apigenin and their glucosides have been shown a good anti-inflammatory activity without the side effects of other anti-inflammatory products. In this paper, we discuss the relation between each structural factor of Citrus flavonoids and the anticancer, anti-inflammatory, and cardiovascular protection activity of Citrus flavonoids and their role in degenerative diseases.
              Article 0 comments Cited 239 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Journal ID (nlm-ta): Int J Mol Sci
                Journal ID (iso-abbrev): Int J Mol Sci
                Journal ID (publisher-id): ijms
                Title: International Journal of Molecular Sciences
                Publisher: MDPI
                ISSN (Electronic): 1422-0067
                Publication date (Electronic): 21 October 2019
                Publication date Collection: October 2019
                Volume: 20
                Issue: 20
                Electronic Location Identifier: 5215
                Affiliations
                [1 ]Biochemistry Division, Chemistry Department, Faculty of Science, Menoufia University, Shebin El-Koom 32512, Egypt
                [2 ]Division of Chemistry and Biotechnology, Graduate School of Natural Science and Technology, Okayama University, Okayama 7008530, Japan
                [3 ]Chemistry Department, Faculty of Science, Menoufia University, Shebin El-Koom 32512, Egypt; asmaakhairybio@ 123456gmail.com
                [4 ]Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, SE 106 91 Stockholm, Sweden; shaden.khalifa@ 123456su.se
                [5 ]Department of Experimental Cancer Medicine (ECM); Novum, 14157 Huddinge, Sweden
                [6 ]Division of Pharmacognosy, Department of Medicinal Chemistry, Uppsala University, Biomedical Centre, Box 574, SE-75123 Uppsala, Sweden
                [7 ]International Research Center for Food Nutrition and Safety, Jiangsu University, Zhenjiang 212013, China
                [8 ]Al-Rayan Research and Innovation Center, Al-Rayan Colleges, Medina 42541, Saudi Arabia
                Author notes
                [* ]Correspondence: bishoy.yousef@ 123456gmail.com (B.E.-A.); hesham.el-seedi@ 123456ilk.uu.se (H.R.E.-S.); Tel.: +20-12-7173-2703 (B.E.-A.); +46-7-0043-4343 (H.R.E.-S.)
                Author information
                https://orcid.org/0000-0001-8520-347X
                https://orcid.org/0000-0002-2519-6690
                Article
                Publisher ID: ijms-20-05215
                DOI: 10.3390/ijms20205215
                PMC ID: 6829218
                PubMed ID: 31640181
                SO-VID: 8b7118cf-3db0-4d95-b4a8-b38ab695e520
                Copyright © © 2019 by the authors.
                License:

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 03 October 2019
                Date accepted : 16 October 2019
                Categories
                Subject: Article

                ScienceOpen disciplines: Molecular biology
                Keywords: liver injury,ccl4,tamarix aphylla,oxidative stress,apoptosis,angiogenesis
                Data availability:
                ScienceOpen disciplines: Molecular biology
                Keywords: liver injury, ccl4, tamarix aphylla, oxidative stress, apoptosis, angiogenesis

                Comments

                Comment on this article

                scite_

                Similar content397

                See all similar

                Cited by4

                See all cited by

                Most referenced authors849

                See all reference authors